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Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase Producing Enterobacterales Undergoing Liver Transplantation (TAILOR)

2026년 8월 6일 업데이트: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Targeted Versus Standard Peri-operative Antibiotic Prophylaxis in Patients Colonized With Carbapenemase-producing Enterobacterales Undergoing Liver Transplantation: a Stepped Wedge Cluster Randomization Trial

This is a multicenter stepped-wedge cluster randomized trial, conducted over a 2-year period at three hospitals. The trial is structured into four phases, each lasting six months. During phase 1 (pre-rollout), all hospitals will use standard antibiotic prophylaxis for all patients. In each of phases 2 to 4, one hospital will switch to targeted antibiotic prophylaxis, so that by phase 4 all hospitals will be using it. The order in which hospitals switch is determined by computer-generated randomization performed centrally by an independent statistician, ensuring each hospital has an equal chance of switching at any given phase and minimizing selection bias.

The goal of this clinical trial is to learn whether targeted antibiotic prophylaxis works better than standard antibiotic prophylaxis at preventing infections in liver transplant patients who carry resistant bacteria called CPE (carbapenemase-producing Enterobacterales). It will also learn about the effects of these antibiotics on gut bacteria.

The main questions it aims to answer are:

  • Does targeted antibiotic prophylaxis reduce the number of CPE infections occurring in the first two weeks after liver transplant, compared to standard prophylaxis?
  • How do targeted and standard antibiotic prophylaxis affect the gut microbiome after transplant?
  • Is there a link between achieving optimal antibiotic blood levels and the risk of developing an infection after transplant?

Researchers will compare targeted antibiotic prophylaxis (chosen based on the specific bacteria each patient carries) to standard antibiotic prophylaxis (used routinely at each hospital) to see which approach better prevents infection.

This study does not involve the administration of any drugs or instrumental examinations beyond those already part of standard clinical care at each center. However, additional blood tests will be performed by collecting one extra blood sample (and a bile sample, if the patient has a Kehr's tube, which is a drain placed in the bile duct after surgery) during blood draws already scheduled as part of routine clinical practice, in order to measure drug levels in the blood. Stool samples will also be collected specifically for the study to investigate the gut microbiome.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

Colonization and infection with carbapenemase-producing Enterobacterales (CPE) have been associated with significant morbidity and mortality in the setting of solid organ transplantation (SOT), and in particular among liver transplant (LT) candidates and/or recipients. Indeed, the prevalence of CPE infection is highest after LT compared with other types of SOT, CPE carriage is the strongest predisposing factor, and CPE carriage/infection has been associated with significant increase in the odds of death across multiple studies. Several strategies have been proposed to reduce CPE infection and associated poor outcome after LT, including active screening, decolonization and targeted perioperative antibiotic prophylaxis (T-PAP). Decolonization is no longer recommended due to its limited benefit and associated adverse events, observed also in a randomized controlled trial on SOT recipients. Recent European guidelines endorsed the performance of active screening for CPE carriage before LT but, due to the lack of evidence, they could not provide a recommendation regarding optimal PAP in CPE carriers. This study addresses a critical unmet need in liver transplantation by evaluating targeted perioperative antibiotic prophylaxis (T-PAP) versus standard perioperative antibiotic prophylaxis (S-PAP) in CPE colonized patients. By using a stepped-wedge cluster-randomized design, it could generate robust, practice-changing evidence on how to reduce early CPE infections, mortality, and healthcare costs. The project is innovative in study design as well as in integrating advanced gut microbiome (GM) and resistome analyses, offering new insights into the GM effects of perioperative antibiotic strategies. The use of therapeutic drug monitoring (TDM) to optimize dosing adds a precision medicine approach. Findings are expected to impact clinical guidelines and improve outcomes for transplant recipients and potentially for other high-risk surgical populations.

The stepped-wedge design is better suited than standard individual randomization for evaluating the potential indirect effects of the T-PAP policy on gut microbiome and liver functionality.

The intervention will consist of targeted perioperative antibiotic prophylaxis (T-PAP) using an agent shown to be active in vitro against the colonizing strain. The specific drug will be selected at the discretion of the local investigator, in collaboration with the attending physician, and, if necessary, discussed with all the study investigators in a dedicated meeting. In the control arm, standard perioperative antibiotic prophylaxis (S-PAP) will be administered according to local protocols. In both arms, prophylaxis will begin 30-60 minutes before surgical incision, following guidelines, and will be discontinued no later than 48 hours post-surgery.

연구 유형

중재적

등록 (추정된)

168

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 이탈리아
    • BO
      • Bologna, BO, 이탈리아, 40138
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • 연락하다:
        • 연락하다:
        • 부수사관:
          • Matteo Rinaldi, MD
    • PI
      • Pisa, PI, 이탈리아, 56126
        • Azienda Ospedaliero Universitaria Pisana
        • 연락하다:
    • TO
      • Torino, TO, 이탈리아, 10126
        • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
        • 연락하다:

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

Inclusion Criteria:

  • Adult (≥18 years) patients colonized with Carbapenemase-Producing Enterobacterales (CPE) undergoing liver transplantation (LT)
  • Informed consent signed by the enrolled patients

Exclusion Criteria:

  • Active infection from any Gram-negative bacteria at the time of LT
  • High risk of donor-derived CPE infection (e.g., donors known to be colonized or infected with CPE at the time of death, or CPE isolated from donor blood or preservation fluid samples)
  • Hypersensitivity to the active substance or to any of the excipients
  • Pregnancy and breastfeeding
  • Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer.
  • History of severe immediate hypersensitivity reactions (e.g., anaphylaxis) to beta-lactam agents (e.g., cephalosporins, carbapenems, or monobactams).
  • Colonization by strains resistant to all Investigational Medicinal Products (IMPs)

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 크로스오버 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Targeted prophylaxis T-PAP

Patients included in the Targeted prophylaxis (T-PAP) arm will be treated using an agent shown to be active in vitro against the colonizing strain. The specific drug will be selected at the discretion of the local investigator, in collaboration with the attending physician, and, if necessary, discussed with all the study investigators in a dedicated meeting.All drugs will be used strictly in accordance with their approved Summary of Product Characteristics (SmPC).

Available drugs that could be used as a T-PAP are:

  • Ceftazidime/avibactam
  • Meropenem/vaborbactam
  • Imipenem/relebactam
  • Cefiderocol
  • Aztreonam
  • Eravacycline
  • Aztreonam/avibactam
의약품: Ceftazidime - Avibactam ( CAZ-AVI)
2g/0.5g powder for concentrate for solution for infusion.Each vial contains ceftazidime pentahydrate equivalent to 2 g ceftazidime and avibactam sodium equivalent to 0.5 g avibactam. For T-PAP, the administration should not exceed 48 hours
의약품: Meropenem-Vaborbactam
1g/1g powder for concentrate for solution for infusion. Each vial contains meropenem trihydrate equivalent to 1 g meropenem, and 1 g vaborbactam. Excipient with known effect: Each vial contains 10.9 mmol of sodium (approximately 250 mg). For T-PAP, the administration should not exceed 48 hours.
의약품: Imipenem+Relebactam

Supplied as a dry powder in a single-dose vial that must be constituted and further diluted using aseptic technique prior to intravenous infusion (IV).

Each vial contains imipenem monohydrate equivalent to 500 mg imipenem, cilastatin sodium equivalent to 500 mg cilastatin, and relebactam monohydrate equivalent to 250 mg relebactam. For T-PAP, the administration should not exceed 48 hours.

의약품: Cefiderocol
Supplied as single use vials containing cefiderocol sodium tosylate, equivalent to 1 g cefiderocol. Excipients include sucrose, sodium chloride and sodium hydroxide. For T-PAP, the administration should not exceed 48 hours.
의약품: Aztreonam
Supplied as a single use vials containing sterile solution of Aztreonam and Arginine and a suitable osmolality adjusting substance in Water for Injection. It contains NLT 90.0% and NMT 120.0% of the labeled amount of aztreonam. For T-PAP, the administration should not exceed 48 hours.
의약품: Eravacycline
Supplied as powder for concentrate for solution for infusion, each vial contains 50 mg of eravacycline. Each vial is for single use only, that must be reconstituted and further diluted using aseptic technique prior to intravenous infusion. For T-PAP, the administration should not exceed 48 hours.
의약품: Aztreonam-Avibactam
Supplied as powder for concentrate for solution for infusion, each vial contains 1.5 g of aztreonam and avibactam sodium equivalent to 0.5 g of avibactam. For T-PAP, the administration should not exceed 48 hours.
실험적: Standard prophylaxis S-PAP

Patients include in the Standard prophylaxis (S-PAP) arm will be treated with standard drugs administered according to local protocols.

Drugs used as S-PAP are:

  • Amoxicillin/clavulanate
  • Piperacillin/tazobactam
  • Tigecycline
의약품: Amoxi Clavulanate
Powder for solution for injection or infusion, supplied as vials of 2000/200 mg. Each vial contains 2000 mg amoxicillin (as amoxicillin sodium) and 200 mg clavulanic acid (as potassium clavulanate). Each vial contains 5.5 mmol (125.9 mg) of sodium and 1 mmol (39.3 mg) of potassium. For S-PAP, the duration should not exceed 48 hours.
의약품: Piperacillin + Tazobactam
Powder for solution, each vial contains amounts of Piperacillin Sodium and Tazobactam Sodium equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of piperacillin, the labeled amounts representing proportions of piperacillin to tazobactam is of 8 : 1. It may contain small amounts of a suitable buffer stabilizer. For S-PAP, the duration should not exceed 48 hours.
의약품: Tigecycline
Powder for solution, each vial should be reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, to achieve a concentration of 10 mg/mL of tigecycline. For S-PAP, the duration should not exceed 48 hours.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
To investigate the impact of T-PAP vs. S-PAP on the incidence of early CPE infection after LT in patients colonized with CPE undergoing LT
기간: Within 14 days after liver transplant
The impact of T-PAP over S-PAP will be calculated comparing the percentage of CPE infections in the first two weeks after LT in the intervention and control group.
Within 14 days after liver transplant

2차 결과 측정

결과 측정
측정값 설명
기간
To investigate the impact of T-PAP vs. S-PAP on the dynamics of gut microbiome after LT in patients colonized with CPE at transplant
기간: At the time of liver transplant, and at 14, 30, 60 and 90 days after liver transplant
Cross-sectional differences between T-PAP and S-PAP groups over time, in GM alpha diversity, composition (relative abundance at different taxonomic levels) and functionality (gene and pathway abundances), will be assessed using the Kruskal-Wallis test, followed by post-hoc Wilcoxon rank-sum tests.
At the time of liver transplant, and at 14, 30, 60 and 90 days after liver transplant
To investigate the relationship between the attainment of optimal pharmacokinetics/pharmacodynamics (PK/PD) target and the occurrence of CPE and non-CPE infections after LT in patients colonized with CPE at transplant
기간: Within 14 days from liver transplant
In order to evaluate the relationship between the attainment of early optimal PK/PD target with agents used for both T-PAP and S-PAP and the occurrence of CPE and non-CPE infections in the post-LT period, TDM of selected agents will be performed at the end of surgical procedure and at 24 hours after starting T-PAP and S-PAP. The relationship between the attainment of optimal PK/PD target and the occurrence of CPE and non-CPE infections will be calculated comparing the percentage of patients developing CPE and non-CPE infections in the first two weeks after LT in the intervention and control group.
Within 14 days from liver transplant
To investigate the impact of T-PAP vs. S-PAP on CPE carriage status
기간: At 30, 60 and 90 days after liver transplant
The impact of T-PAP vs S-PAP on CPE carriage status will be calculated comparing the percentage of patients colonized with Carbapenem-producing Enterobacterales (CPE) at 30, 60 and 90 days after LT in the intervention and control group.
At 30, 60 and 90 days after liver transplant
To investigate the development of bacterial infections
기간: At 30, 60 and 90 days after liver transplant
The impact of T-PAP vs S-PAP will be calculated comparing the percentage of patients diagnosed with a bacterial infection at 30, 60 and 90 days after LT in the intervention and control group.
At 30, 60 and 90 days after liver transplant
To investigate all-cause mortality
기간: At 30, 60 and 90 days after liver transplant
The impact of T-PAP vs S-PAP will be calculated comparing the percentage of patients who died from any cause at 30, 60 and 90 days after LT in the intervention and control group.
At 30, 60 and 90 days after liver transplant
To investigate the safety of T-PAP versus S-PAP
기간: During prophylaxis administration or within 7 days from the initiation of administration
The rates of adverse events (e.g. neurotoxicity) in the intervention and in the control groups will be computed.
During prophylaxis administration or within 7 days from the initiation of administration

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

IRCCS Azienda Ospedaliero-Universitaria di Bologna

수사관

  • 수석 연구원: Maddalena Giannella, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 10월 1일

기본 완료 (추정된)

2029년 6월 30일

연구 완료 (추정된)

2029년 9월 30일

연구 등록 날짜

최초 제출

2026년 6월 19일

QC 기준을 충족하는 최초 제출

2026년 8월 6일

처음 게시됨 (실제)

2026년 8월 12일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 8월 12일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 8월 6일

마지막으로 확인됨

2026년 6월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • TAILOR
  • 2025-523453-34-00 (씨티스)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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